DESCRIPTION (Applicant's Description) Muscle invasive bladder cancers are heterogeneous both in terms of cell kinetic attributes and response to radiotherapy. The hypotheses of this proposal are that the cell kinetic status of muscle invasive bladder cancers, as determined by potential doubling (Tpot) and surrogate immunohistochemical (IHC) tests, correlates with local control and that accelerated concomitant boost radiotherapy is feasible, safe and results in improved local control and good quality of life in medically inoperable patients. The specific aims are to: (1) determine cell kinetics patterns of transitional cell carcinoma of the bladder (TCCB) using Tpot, (2) develop a method for determining cell growth kinetics using a panel of surrogate IHC tests to replace Tpot, (3) determine the safety (toxicity) and efficacy (local regional tumor control) of accelerated concomitant boost pelvic radiotherapy, a new radiotherapy treatment schedule for TCCB, (4) determine the relationship between the tumor growth kinetics and the clinical outcome of patients with TCCB treated with accelerated concomitant boost radiotherapy, (5) study the effect of this treatment regimen on patient's quality of life. There are five institutions participating in this single-arm Phase 11 study of accelerated concomitant boost radiotherapy for treatment of patients with muscle invasive transitional cell carcinoma of the bladder (TCCB). The study schema includes intravenous BrdU infusion (200 Mg/M2) and maximal (aggressive) transurethral resection of the bladder tumor (TURBT), followed by accelerated concomitant boost radiotherapy to a dose of 69.9 Gy over 5.5 weeks. The technique of concomitant boost was developed using a large cohort of head and neck cancer patients, and is designed to accelerate the treatment during the last 2.5 weeks by administering radiation treatments twice-a-day. With conventional radiotherapy (at dose rate of 180-200 cGy and total doses of approximately 6500 cGy) the local regional control rate for T2 to T4 bladder cancer is approximately 45 percent. Concomitant boost accelerated radiotherapy could improve the local control rate to over 60 percent (Plataniotis, et al, 1994). Cell kinetics has been demonstrated in previous studies, in patients with Head and Neck cancer, to have predictive value in determining which patients are most likely to benefit from accelerated radiotherapy. We will use an established method (Tpot) of cell kinetic analysis and a now and less complex method, IHC, to determine the rate of tumor growth using biopsies obtained on patients prior to initiation of radiotherapy. We will collect toxicity information and compare these to published data on altered fractionation schedules implemented in Europe and the United States. Quality of Life will be also assessed during this trial.